Since inception in 1995, the University of Michigan (UIVI) Prostate SPORE has endeavored to tap the vast intellectual and physical resources of the UM community to decrease the morbidity and mortality of prostate cancer (PCa). The UIVI Prostate SPORE supports an interactive group of basic and clinical investigators in a translational research program that has led to major discoveries in the diagnosis, prevention and treatment of prostate cancer. Successful translation of discoveries in the most recent grant period include: 1) development of a urine test for prostate cancer which is now offered in CLIA reference laboratories (Sci TransI Med. 2011); 2) ETS gene fusion driven PCa that are susceptible to PARP inhibitor therapy (Cancer Cell 2011) which initiated a randomized Phase II trial (NCTOI576172); 3) germline mutations in HOXB 13 gene that conferred increased risk for PCa (N Engl J Med. 2012). This is being developed as a test for assessing PCa risk; 4) the first study describing the mutational landscape of metastatic castrate resistant prostate cancer (CRPC) (Nature 2012,) and; 5) Cabozantinib was shown to have efficacy and decrease bone pain in prostate cancer patients with bone metastasis (J Clin Oncol. 2013). These bench-to-bedside applications were aided by horizontal collaborations with the Dana Farber, Baylor, Mayo Clinic and Johns Hopkins Prostate SPOREs as well as the EDRN and vertical collaborations with SWOG and biotech companies. This application consists of four multidisciplinary projects: Project 1: A Precision Medicine Approach to Elucidate Mechanisms of Progression and Resistance to Therapy in Advanced PCa; Project 2: Mechanisms of Sensitivity and Resistance to Cabozantinib in CRPC; Project 3: Development of Novel BET Bromodomain Inhibitors for the Treatment of Advanced PCa; Project 4: Development of IncRNAs as PCa Biomarkers in Urine. These projects are complemented by ongoing, successful Career Development and Developmental Research Programs. The projects and programs are supported by a strong ongoing institutional commitment of money and space as well as three cores: Administration, Biostatistics, and Tissue/Informatics. The UM Prostate SPORE program continues to place premiums on rigorous scientific review of its translational research programs, pairing of basic and clinical investigators, drawing on expertise of scientists from within and fro outside the prostate cancer field, and utilizing flexibility to fund promising new research approaches. The interaction of our multidisciplinary group of investigators clearly makes the Prostate SPORE program at the UMCCC is greater than the sum of its individual parts.